The present invention relates to a process for preparing substituted coumarins. More particularly, the present invention relates to a process for preparing substituted coumarins using polyaniline salts as catalysts.
Coumarins are an important group of naturally occurring compounds, widely distributed in the plant kingdom and have been produced synthetically for many years for commercial use. Members of this group display a broad range of applicationsxe2x80x94as fragrances, pharmaceuticals, additives to food, cosmetics, agrochemicals, optical brightening agents, dispersed fluorescent and tunable dye lasers, and biological activities like anthelmintic, hypnotic, insecticidal and anticoagulant properties. Coumarins also act as intermediates for the synthesis of fluorocoumarins, chromones, coumarones, and 2 -acylresorcinol. [Seexe2x80x94Boisde et al, Kirk-Othmer Encyclopedia of Chemical Technology (Ed, Jacqline I. Kroschwitz), 4th Edition, Vol.7, Pages 647-658 and references therein]. Coumarin and some of its derivatives have been identified in plants and many of them have been synthesized and studied for their physiological activity. 7-hydroxy coumarin, known as umbelliferone, occurs naturally in gum resins of Umbelliferae and is an important coumarin metabolite. It is readily manufactured from resorcinol and maleic or fumaric acid. Derivatives of umbelliferone have attracted interest as sunburn preventives on account of their wide spectrum of UV absorption.
7-hydroxy-4-metylcoumarin (xcex2-methylumbelliferone) is used as fluorescent brightener, efficient laser dye for pulsed and SW operation, standard for the flurometric determination of enzyme activity, as a starting material for the preparation of an insecticide (Hymerocromone), as precursor for furano coumarins and many other derivatives of substituted coumarins and as analytical reagents. 5,7-dihydroxy-4-methylcoumarin is used in suntan oils as sunscreen, and in wall paints as whitening agents. Coumarin and its derivatives can be synthesized by various methods which include Perkin reaction (Donnelly et al, Tetrahedron, 1968, vol 24, p-2617-2622), Knoevenagel reaction (Franca Bigi et al, J. Org. Chem., 1999, vol 64, p-1033-1035), Wittig reaction (Yavari et at, Tetrahedron Lett., 1998, vol 39, p-2391-2392), Pechmann reaction (John et al, J. Org. Chem., 1961, vol 26, p-240-242) and Reformatsky reaction. Among these methods, Pechmann reaction is the most widely used method for the preparation of substituted coumarins since it proceeds from very simple starting materials and gives good yields of various substituted coumarins.
Substituted coumarins have been prepared using various reagents such as H2SO4, POCl3 (Ahmad et al, Proc. Indian Acad. Sci., 1937, vol.5A, p-277-284), AlCl3 (Das gupta et al, J. Chem. Soc., 1969, p-29-33), Cation exchange resins (John et al, J. Org. Chem, 1961, vol 26, p-240-242), trifluoro acetic acid (Woods et al, J. Org. Chem., 1962, vol 27, p-3703-3705), Montmorillonite clay (Bhattacharyya et al, Ind. J. Chem., 1992, vol 31B, p628), solid acid catalysts (Bekkum et al, J. Chem. Soc., Chem. Commun., 1995, p-225-226), W/ZrO2 solid acid catalyst (Reddy et al, Synth. Commun., 2001, vol 31 (23), p-3603-3607), Chloroaluminate ionic liquid (Khadilkar et al, Synlett, 2002, No 1, p-152-154) and Nafion-H catalyst (Chaudhari, Chem. Ind., 1983, p-569-570).
Condensation is one of the most fundamental and important reactions in organic synthesis. Conventionally, the processes of making coumarins can be carried out by:
(a) Liquid-phase reaction utilizing a liquid catalyst: This type of process utilizes liquid phase acids, such as sulfuric acid, phosphoric acid, or sulfonic acid, as catalysts.
(b) Liquid phase reaction utilizing a solid catalyst: This type of processes typically utilizes inorganic salts, cation exchange resin and solid acid catalyst etc.
One problem associated with liquid-phase reaction using liquid-catalyst, is that the acidic catalysts of sulfuric acid or sulfonic acid can cause corrosion problems to the reactor. These liquid acid catalysts are also discharged along with reaction products, thus causing sever waste disposal and pollution problems.
The drawback of using mineral acids as catalysts are: (i) Catalyst can not be reused, (ii) Disposal of acid is not environmentally safe and it is not economical, (iii) Low selectivity is frequently observed, (iv) Corrosion of the reaction vessel and reactors, (v) Not easy to handle and (vi) High inventory of the catalyst.
The solid-catalyst in liquid-phase reaction, which typically utilizes a cation exchange resin as catalyst, ameliorates the corrosion and waste disposal problems experienced with the liquid-catalyst in liquid-phase processes, and results in simplified separation procedure required between the reaction product and catalysts. However, cation exchange resins typically exhibit relatively poor heat-resistance, and they often lose substantial activity after being subject to heat. Once the catalytic activity of the cation exchange resins is reduced, it is difficult to be regenerated.
The main object of the present invention is to provide a process for the preparation of substituted coumains using polyaniline salts as catalysts, which obviates the drawbacks as detailed above.
Accordingly, the present invention relates to a process for the preparation of substituted coumarin using polyaniline salts as catalysts, which comprises the reaction between phenols and keto esters in presence of catalysts in the temperature range from 110 to 170xc2x0 C. for the period of 3 to 24 hrs., separating the product by conventional method from the reaction mixture.
In an embodiment of the present invention, the phenols used is selected from resorcinol, phloroglucinol and pyrogallol.
In an another embodiment of the present invention, the keto esters used is selected from methyl acetoacetate, ethyl acetoacetate and phenyl acetoacetate.
In an yet another embodiment of the present invention, the catalysts is a polyaniline salt selected from polyaniline-sulfate, polyaniline-hydrochloride, polyaniline-nitrate, polyaniline-perchlorate, polyaniline-sodium bisulfate, polyaniline-p-toluene sulfonate, polyaniline-trifluoroacetate and polyaniline-sulfosalicylate system.
In still yet another embodiment of the present invention, the reaction is carried out in the temperature range from 110 to 170xc2x0 C.
In still yet another embodiment of the present invention, the reaction is carried out for a period of 3 to 24 hrs.
In still yet another embodiment of the present invention, the catalyst amount used is 10% to 30% with respect to phenols.
In still yet another embodiment of the present invention, the amount of keto ester used is 1, 1.2, 1.5, 2.0, 3.0 equivalent with respect to one equivalent of phenols.
In still yet another embodiment of the present invention, the solvent is selected from toluene, xylene, chlorobenzene and p-chloro toluene.
These embodiments will be apparent from the ensuing detailed description of the present invention.
The process of preparation of substituted coumarins is carried out by reacting phenols with keto esters in presence of catalyst and then removing the catalyst by conventional methods. The substituted coumarins can be isolated such as filtration followed by isolation of product by conventional methods.
The novelty of the invention resides in the use of polyaniline salt as catalyst in the preparation of substituted coumarins. The use of polyaniline salts as catalysts provides the following advantages: (i) separation of catalyst from a reaction mixture is easy, (ii) repeated use of catalyst is possible, (iii) there is no problem for the disposal of used catalyst as they are environmentally safe and (iv) preparation of the catalyst is a straight forward synthetic route.